Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Is Associated with HLA-A*3303 and HLA-DPB1*0501.

We determined the genetic association between specific human leucocyte antigen (HLA) loci and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Our results showed that autoimmune GFAP astrocytopathy was associated with HLA-A*3303 (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.32-3.06, p = 0.00072, padj. = 0.046) and HLA-DBP1*0501 (OR = 0.51, 95% CI = 0.36-0.71, p = 0.000048, padj. = 0.0062). Moreover, HLA-A*3303 carriers with the disease had a longer hospital stay (p = 0.0005) than non-carriers. This study for the first time provides evidence for a role of genetic factor in the development of autoimmune GFAP astrocytopathy. ANN NEUROL 2024;95:901-906.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Meningoencephalitis associated with GAD65 autoimmunity.

Background: Encephalitis has been recognized in patients with autoimmunity related to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) antibodies; however, patients with meningoencephalitis associated with those antibodies have been rarely identified in the medical literature. We aimed to define the frequency, clinical features, response to therapy, and functional outcomes of patients with meningoencephalitis associated with GAD antibodies. Methods: We retrospectively studied consecutive patients attending a tertiary care center for evaluation of an autoimmune neurological disorder from January 2018 to June 2022. The modified Rankin Scale (mRS) was used to assess the functional outcome at the last follow-up. Results: We evaluated 482 patients with confirmed autoimmune encephalitis during the study period. Four among the 25 patients with encephalitis related to GAD65 antibodies were identified. One patient was excluded owing to the coexistence of NMDAR antibodies. Three male patients aged 36, 24, and 16 years had an acute (n = 1) or subacute (n = 2) onset of confusion, psychosis, cognitive symptoms, seizures, or tremor. No patient had fever or clinical signs of meningeal irritation. Mild pleocytosis (<100 leukocytes/106) was identified in two patients, whereas one patient had normal CSF. Following immunotherapy with corticosteroids (n = 3) or intravenous immunoglobulin (n = 1), significant improvement was observed in all three cases, achieving a good outcome (mRS 1) in all cases. Conclusion: Meningoencephalitis is an uncommon presentation of GAD65 autoimmunity. Patients present with signs of encephalitis but with meningeal enhancement and have good outcomes.

3-Hz Postural Tremor in MSA-C and SCA: Revisiting an Old but Underestimated Cerebellar Sign by Posturography.

The aim of this study is to evaluate the prevalence and electrophysiological features of 3-Hz postural tremor in multiple system atrophy-cerebellar type and spinocerebellar ataxia. A static posturography examination was administered to 37 persons with spinocerebellar ataxia, 58 others with the cerebellar type of multiple system atrophy, and 53 healthy controls. During the sensory organization tests of 5 multiple system atrophy patients, surface electromyograms were recorded from bilateral tibialis anterior and medial gastrocnemius muscles. The patients with multiple system atrophy had, on average, significantly higher scores on the International Cooperative Ataxia Rating Scale and significantly greater prevalence of cross sign. Almost 80% of them fell during the posturography testing compared with two-thirds of the spinocerebellar ataxia patients. Twenty-seven percent of the spinocerebellar ataxia patients and 82.8% of those with multiple system atrophy displayed postural tremor with a frequency of approximately 3 Hz. The tremor's frequency tended to be lower in the spinocerebellar ataxia patients. The surface electromyography revealed highly coherent tremor activity at about 3 Hz in the patients' bilateral tibialis anterior and alternating firing in the bilateral antagonist muscles. Combining cross sign with a subject's static score of the International Cooperative Ataxia Rating Scale and occurrence of the tremor produced an indicator able to differentiate the two conditions with a sensitivity of 87.9% and a specificity of 89.2%. The area under the receiver operating characteristics curve for the indicator was 0.942. Three-hertz postural tremor is relatively characteristic of cerebellar type of multiple system atrophy and appears at an early stage of the disease. Identification of the tremor by posturography will facilitate its diagnosis.

Comparison of magnetic resonance spectroscopy (MRS) with arterial spin labeling (ASL) in the differentiation between mitochondrial encephalomyopathy, lactic Acidosis, plus stroke-like episodes (MELAS) and acute ischemic stroke (AIS).

To compare the utility and limitation of magnetic resonance spectroscopy (MRS) and arterial spin labeling (ASL) in the differentiation between mitochondrial encephalomyopathy, lactic acidosis, plus stroke-like episodes (MELAS) and acute ischemic stroke (AIS), a retrospective review of 17 MELAS and 26 AIS patients were performed. In all patients both MRS and ASL scans were performed within 1 week after admission. Demographic, clinical, laboratory and MR imaging data were reviewed and compared between the two groups. Compared with AIS, MELAS patients had a younger age of onset, a longer disease duration, a higher occurrence of epilepsy attack, occipital and parietal lesions, and dilated cerebral arteries (P < 0.05). In all MELAS patients lactate peak and hyperperfusion of the lesion was revealed. However in AIS lactate peak was observed in only 69.2% and hyperperfusion was observed in only 34.6% ischemic lesions (P < 0.05). Choline/Creatine ratios and Lactate/Creatine ratios were higher in AIS, while in MELAS cerebral blood flow and lesion-normal perfusion ratio was much higher (P < 0.05). No correlations was found between metabolite ratios and perfusion parameters in either group (P > 0.05). Area under curve (AUC) of perfusion for the differentiation between MELAS and AIS was 0.958 (P < 0.001). The cut-off value was 2.075, with a sensitivity of 88.2% and a specificity of 96.2%. AUC of Lactate/Creatine ratio was 0.469 (P = 0.737). Utility of MRS is limited in the differentiation between MELAS and AIS, while MR perfusion profiles are much more sensitive and specific.

Lesions of the posterior limb of the internal capsule in neuromyelitis optica spectrum disorder.

Posterior limb of the internal capsule lesions (PLICL) are one of the MRI features of neuromyelitis optica spectrum disorder (NMOSD). However, there is no evidence that such lesions are pathogenically related to NMOSD. We retrospectively analyzed features of PLICL in NMOSD, and other central nervous system inflammatory disorders, in 561 patients. We also examined the pathological samples of six patients. Of the 561 patients investigated, PLICL were found in 65 patients (11.6%). Lesions were bilateral in 26 cases (40%) and unilateral in 39 cases (60%). Unilateral lesions were mainly located on the left side (74.3%, 29/39). Of the 65 patients with PLICL, 46 patients had NMOSD (70.8%) and were positive for anti-aquaporin (AQP4-IgG), four had NMOSD (6.2%) and were AQP4-IgG negative, 10 patients had multiple sclerosis (MS), three patients had NMDAR encephalitis, and two had autoimmune meningoencephalitis. Of the six patients whose pathological samples were evaluated, all had PLICL and were negative for AQP4-IgG, and none had pathological NMOSD lesion features. These cases included three patients with multiple sclerosis, one with anti-N-methyl-D-aspartate receptor encephalitis, and two with autoimmune meningoencephalitis. In conclusion, PLICL are found not only in patients with NMOSD, but also in MS and other disorders.

[Application of near-infrared spectrum technology to research of weathering of red sandstone relics].

In the present paper, with near infrared spectroscopy technology, the weathering mechanism of red sandstone relics was studied. Six groups of red sandstone samples were analyzed using near infrared spectroscopy technology. The results show that the near-infrared spectroscopy technology can analyze the material composition of red sandstone before and after weathering, aiming to explore their components changed. So it is a quick and efficient means of research with characteristic of less measurement sample and speed and non-damage and being pollution-free compared with other research techniques. All the characteristic shows that it is also well for studying other stone cultural relics. Especially for those with sampling difficulty and treasure valuable, non-destruction of stone cultural relics is particularly important. So with time advancing, near infrared technology as a research means of stone relics, its meaning will be more prominent.